1 Chest X-ray 450521V201 CT scan Subclavian artery 450521V201 - PDF document

Case presentation Paul De Leyn, MD, PhD Thoracic Surgery University Hospitals Leuven Belgium Perspectives in Lung Cancer Brussels 6-7 march 2009 LEUVEN LUNG CANCER GROUP Department of Thoracic Surgery P. De Leyn,W. Coosemans, H. Decaluwé, Ph. Nafteux, D. Van Raemdonck, G. Decker, T. Lerut Department of Pneumology J. Vansteenkiste, K. Nackaerts, C. Dooms Department of Radiotherapy Y. Lievens Department of Nuclear Medicine S . Stroobants Department of Radiology W. Dewever • 02-2003 • 57-year lady • 3 months pain in left schoulder and upper arm – Antiflogistics – Morfine • Horner syndrome • Medical history – 20 packyears 450521V201 1

Chest X-ray 450521V201 CT scan Subclavian artery 450521V201 Investigations • Laboratory – CEA : 12.2 μ g/L (< 3,4 μ g/L ) • Bronchoscopy : normal – Aspirate : normal – Transbronchial biopsy : normal – Transthoracic puncture : large cell carcinoma • Bone scintigraphy : normal • PET scan : T positive, N0M0 • Pulmonary function test : normal 450521V201 2

Diagnosis • Pancoast tumor • cT4 (Horner, subclavian artery) N0M0 THERAPY? 450521V201 Further therapy? 1. Chemotherapy 2. Radiotherapy 3. Chemoradiotherapy 4. Induction radioTx + surgery 5. Induction chemoradioTx + surgery 450521V201 Superior sulcus tumours - Pancoast tumor Major challenge : control of locoregional disease Low complete resectability rate despite major procedures Preoperative RT (30-35 Gy) T3N0 : R0 : 66%, T4N0 : R0 : 18%, 5-year survival : 12% Rush et al., J Thorac Cardiovasc Surg 2000;119:1147-1153 3

Induction chemoradiotherapy for pancoast (SWOG 9416) • Inclusion : cT3-T4NO (mediast : neg) n=110 • Concurrent chemoradiotherapy (cis, etoposide; 45 gy) C t h di th ( i t id 45 ) • Surgery in responders and stable disease Rusch et al. J Thorac Cardiovasc Surg, 2001;11:472-83 Rusch et al. J Clin Oncol 2007;25:313-318 Induction chemoradiotherapy for pancoast (SWOG 9416) Rush et al. J Thorac Cardiovasc Surg, 2001;11:472-83 Rush et al. J Clin Oncol 2007;25:313-318 Induction chemoradiotherapy for pancoast (SWOG 9416) • Complete resectability : 75% • Pathological complete response or minimal microscopic disease : 65% – Overall survival (5-yr) : 44% – Survival in R0 resections (5-yr) : 54% Rusch et al. J Thorac Cardiovasc Surg, 2001;11:472-83 Rusch et al. J Clin Oncol 2007;25:313-318 4

Induction chemoradiotherapy for pancoast (SWOG 9416) 54% (R0 resections) Rusch et al. J Thorac Cardiovasc Surg, 2001;11:472-83 Rusch et al. J Clin Oncol 2007;25:313-318 • 20-02-2003 : Cervical mediastinoscopy – Negative at levels 7, 4L, 4R and 2R • Concommitant chemoradiotherapy (start 10-03-2003) – Cisplatin-etoposide (2 courses) – 45 gy (25 fractions of 1.8 gy) 45 gy (25 fractions of 1.8 gy) • Reevaluation 18-04-2003 – No pain – CT : yT4N0M0 450521V201 CT after induction chemoradioTx yT4N0M0 450521V201 5

CT after induction chemoradioTx yT4N0M0 450521V201 Further therapy? 1. Surgery 2. Further radiotherapy 3. Stop therapy 450521V201 • 06-05-2003 : Left posterolateral thoracotomy (Paulson incision) • Upper lobectomy + chest wall resection (rib 1 + 2). No reconstruction of chest wall • Pathology : fibrosis +++ Some small islands of viable tumor pT2N0M0, complete resection 450521V201 6

Giant cell Sclerosis, macrophages Cholesterol Necrosis 450521V201 Viable tumor cells Giant cell Sclerosis, macrophages, cholesterol 450521V201 CT scan is poor predictor of response SWOG 9416 cT3-T4N0M0 pancoast tumors (n=110) Complete resectability : 75% 65% of specimens showed a pathologic complete response or minimal microscopic disease 32 (36%) pathologic complete response 17 partial response on CT 15 stable disease on CT Rusch et al. J Thorac Cardiovasc Surg, 2001;11:472-83 Rusch et al. J Clin Oncol 2007;25:313-318 7

• No postoperative problems (hospital stay : 11 days) • 2 adjuvant courses of cisplatinum-etoposide cisplatinum etoposide (start 26-05-2003) • March 2008 : No evidence of disease (CEA : 1,6 μ g/L) 450521V201 Materials and methods • April 2002 – februari 2008 • 32 patients (prospective, consecutive) • cT4 tumor (17) – Pancoast 15 (cT3-4) cT4 Pancoast Pulmonary artery : P l t 5 5 cT3 : 5 Atrium : 5 cT4 : 10 Aorta : 3 Extens mediastinal infiltration : 2 Recurrent laryngeal nerve : 1 Subclavian artery : 1 • N0 – M0 (PET or CT/PET and mediastinoscopy) De Leyn et al, J Thorac Oncol 2009;4:62-8 De Leyn et al, J Thorac Oncol 2009;4:62-8 8

Postoperative morbidity/mortality • Mean hospital stay : 9.2 days • No hospital mortality • ICU : 1 patient • No bronchopleural fistulae or empyema De Leyn et al, J Thorac Oncol 2009;4:62-8 De Leyn et al, J Thorac Oncol 2009;4:62-8 86% 60% De Leyn et al, J Thorac Oncol 2009;4:62-8 9

Remaining questions • Improve induction therapy? – Increase radiation dose – Hyperfractionated accelerated RT – Third-generation chemotherapy? g py • Profyllactic cranial irradiation? High dose radiotherapy in trimodality treatment of pancoast tumors N = 36 Preoperative chemoradiation (mean total radiation dose : 56.9 gy) dose : 56.9 gy) R0 resection : 97% Pathological CR : 40% Operative mortality : 2.7% Kwong et al, J Thorac Cardiovasc Surg 2005;129:1250-7 Prohyllactic Cranial irradiation? Single site brain metastasis is most common site of recurrence (>40%) Significant reduction in incidence of brain metastasis in patients with operable stage-IIIA NSCLC undergoing trimodal treatment Control : 35% PCI : 7.8% Rusch et al. J Clin Oncol 2007;25:313-318 Kwong et al, J Thorac Cardiovasc Surg 2005;129:1250-7 Pöttgen et al., J Clin Oncol 2007;25:4987-92 10

Conclusion • Trimodality treatment is feasible with low morbidity and mortality • High complete resectablity • CT scan is poor predictor of response. Both patients with response or stable disease on CT should be explored • Prophyllactic PCI? • Multidisciplinary approach K.U. Leuven, Belgium University Hospital Gasthuisberg Leuven Lung Cancer Group (www.LLCG.be) 11